IDENTIFICATION OF MAJOR CHEMICAL CONSTITUENTS AND THEIR METABOLITES IN RAT PLASMA AND VARIOUS ORGANS AFTER ORAL ADMINISTRATION OF EFFECTIVE XIANG-FU-SI-WU DECOCTION FRACTION BY UPLC-Q-TOF-MS AND METABOLYNX

Abstract

A simple and specific UPLC-Q-TOF-MS method with automated data analysis (MetaboLynx) has been developed and applied for the primary investigation of metabolism pathway of active Xiang-Fu-Si-Wu Decoction fraction (XFSW-8). Through the online ESI-MS^E analysis and automated data analysis (MetaboLynx), a total of fifteen constituents have been identified or tentatively characterized from the nine tested samples after oral administration of XFSW-8. Six parent compounds and nine metabolites were identified in blood and eight organs. Methylates/demethylates sulfation, glucuronidation, sulfation, and glucuronidation conjugates were the major metabolic pathways of alkaloids in XFSW-8 in vivo. The present study provided important information regarding the metabolism of alkaloids in Xiang-Fu-Si-Wu Decoction which will be helpful for fully understanding of the mechanism of action of this Chinese medicine. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Liquid Chromatography and Related Technologies to view the free supplemental file.

Keywords:

• identification
• metabolites
• MetaboLynx
• rat plasma and organs
• UPLC-Q-TOF-MS
• Xiang-Fu-Si-Wu decoction

ACKNOWLEDGMENT

This research was financially supported by the Construction Project for Jiangsu Engineering Center of Innovative Drug from Blood-conditioning TCM Formulae. This work was also supported by Key Research Project in Basic Science of Jiangsu College and University of China (No. 06KJA36022; No. 11KJA360002); and the National Key Technology R&D Program (2008BAI51B01). It was also a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (ysxk-2010) and supported by the Open Project Program of Chinese formulae key subject of Nanjing University of Chinese Medicine (2011FJ006). We are also pleased to thank Waters China Ltd. for technical support.

Notes

*Further confirmation in comparison with authentic standards.

Rt, retention time; m/z, mass-to-charge ratio.

UHPLC retention times, positive ion MS^E fragmentation patterns and identification of metabolites isolated from rat plasma and various organs after oral ingestion of XFSW-8. Data are representative for three independent experiments.

The number of chemical constituents and their metabolites was presented in brackets: 1. Plasma (6); 2. Brain (6); 3. Ovary (5); 4. Uterus (8); 5. Kidney (9); 6. Spleen (8); 7. Lung (9); 8. Heart (8); and 9. Liver (12).